THE ANIMAL PHARMACOLOGY OF BUPRENORPHINE, AN ORIPAVINE ANALGESIC AGENT

Abstract

1 The general pharmacology of buprenorphine, a potent analgesic agent derived from oripavine, is described. 2 After acute administration of buprenorphine, the spontaneous locomotor activity of mice was increased; rats displayed stereotyped licking and biting movements; behavioural depresssion was marked in guinea-pigs but mild in rhesus monkeys. The behaviour of cats was unchanged. 3 In general, buprenorphine reduced heart rate but had no significant effect on arterial blood pressure in conscious rats and dogs. 4 In anaesthetized, open-chest cats buprenorphine (0.10 and 1.0 mg/kg, i.v.) caused no major haemodynamic changes. 5 Buprenorphine (0.01-10 mg/kg, i.a.) and morphine (0.30-30 mg/kg, i.a.) increased arterial Pco₂ values and reduced Po₂ values in conscious rats. With doses of buprenorphine greater than 0.10 mg/kg (a) the duration of respiratory depression became less, (b) ceiling effects occurred such that the maximum effects produced were less than those obtained with morphine. 6 Buprenorphine was a potent and long-lasting antagonist of citric acid-induced coughing in guinea-pigs. 7 At a dose level 20 times greater than the ED₅₀ for antinociception (tail pressure), morphine suppressed urine output to a greater extent than the corresponding dose of buprenorphine in rats. 8 Over the range 0.01-1.0 mg/kg (s.c.), buprenorphine slowed the passage of a charcoal meal along the gastrointestinal tract in rats. After doses in excess of 1 mg/kg, the meal travelled increasingly further such that the distances measured after 10 and 30 mg/kg did not differ significantly from control values. In contrast, the morphine dose-response relationship was linear.